Various medical techniques have been used to treat tissue disruptions, including wounds to dermal tissue and disruptions to tissues in other parts of the body. Some objectives for the treatment of wounds are to achieve wound closure and promote the proper formation of new tissue at the wound site. Without some type of medical intervention it can be very difficult for the body to heal a wound in a manner that results in minimal subsequent tissue alteration. If the extent of damage to underlying vascular tissues is significant, vascularization is compromised and oxygen cannot be supplied to the wound in sufficient quantities for good healing. Infection at the wound site can also create problems and slow down cellular processes involved in the healing process. In some cases other body problems (ulcers) make it difficult for the healing process to proceed leading to chronic wounds.
Conventional methods that facilitate wound healing involve the use of wound dressings. Currently, numerous occlusive types of wound dressings are used or suggested for treatment. These include polyurethane films, hydrocolloidal particles bound to polyurethane foams, hydrogels, hydrophilic and hydrophobic foams, nonwoven composites of fibers from calcium alginate, and cellophane.
More recent interest for the treatment of wounds, especially deep or cavernous wounds, has focused on compositions that polymerize and foam in situ. These compositions are able to produce a one-piece absorbent foam and fill the wound. Success of these in situ compositions and treatments however, has been limited. Foam forming systems contemplated for in situ wound treatment suffer from one or more of the following drawbacks: lack of biocompatible foam forming materials or foamed product; expensive materials; significant foam set-up times; and insufficient structural properties of formed foams (such as porosity, structural integrity, strength, and flexibility).
Although it is believed that porous foamed materials can be useful for tissue healing, many traditional techniques for producing foams do not use biocompatible starting materials. For example, although polyurethane foams are widely used in various areas of technology, there are fundamental concerns with the biocompatibility of the components used to make polyurethane foams. The preparation of foamed polyurethanes generally involves the use of diisocyanates, which can be toxic and can cause a significant inflammatory response. Toxic catalytic systems have also been used for the preparation of polyurethane foams. Even the application of pre-formed polyurethane foams to tissue can be problematic if unreacted diisocyanate material is present in the foam and leeches into tissue intended to be treated. Furthermore, polyurethane forms are generally not biodegradable over periods of time useful for tissue healing processes.
Another challenge for the preparation of biocompatible foams relates to the reaction chemistries needed to produce a crosslinked matrix of polymeric materials and gas bubbles as the polymeric materials crosslink to form the foam. The production of polyurethane foams from isocyanate starting materials is typically robust and reliable, resulting in well formed porous foams. Polyurethane foams are typically prepared by the reaction of isocyanates with active hydrogen-containing compounds (such as polyhydric alcohols), in the presence of small quantities of water. Urethane polymer formation of isocyanates with alcohols is accompanied by the production of gas. The gas required from the foam production comes from the carbon dioxide produced from the reaction of the isocyanate group with water. The carbon dioxide diffuses into bubbles in the reaction mixture and causes expansion of the polymerizing material to make a foam. The gas-producing reaction is linked to the polymerization reaction (and thereby occurs simultaneously).
However, the production of foams using non-isocyanate chemistries can be considerably more difficult. In many other systems, the chemistry of crosslinking of the polymeric materials is not linked to the chemistry of gas bubble production. This, in turn, makes the production of other types of polymeric foams considerably more challenging, especially where it is desired to form the foams on a tissue site in a short period of time.
Crosslinked collagen-mucopolysaccharide composites have been described as materials suitable for the production of porous foams. In these foams, the mucopolysaccharide used is alginate, which can becomes ionically crosslinked using a cation, such as calcium. In terms of biocompatibility, these materials can provide an improvement over materials used to make polyurethane foams, but suffer from a number of shortcomings. For example, foams produced from collagen-alginate materials can have rather poor porous structures. Collagen-alginate foams produced using conventional techniques (see, for example, U.S. Pat. No. 5,840,777) are often very thin (less than 5 mm) with thicker structures becoming prone to collapsing upon itself. In addition, for in situ application, cationic crosslinking of the collagen-alginate materials can take a considerable period of time (e.g., from two to five minutes). This may be unacceptable in many medical procedures where the material is desired to foam very quickly (such as in a period of time of less than 20 seconds). Furthermore, with this slow crosslinking it can be difficult to coordinate gas generation with polymerization. Gas may escape from the compositions as the materials ionically crosslink, resulting in an insufficient porous structure.
Because of these problems collagen-alginate foams are preferably made by freeze drying. Freeze drying techniques, however, are not practical for the production of in situ formed foams. Freeze dried foams also suffer the disadvantage of shrinking considerably and irreversibly when brought into contact with liquids, such as an aqueous solution. Such shrinkage causes closure of the pores and makes the material less useful in the applications where the high level of porosity is required or preferable. The problems of shrinkage and pore collapse suffered by crosslinked collagen-mucopolysaccharide materials are not unique to the materials. A wide variety of natural and synthetic polymers also suffer these mechanical problems when placed in contact with liquids. Furthermore, a foam created from crosslinked collagen-alginate materials can be very difficult to degrade when placed in contact with tissue.